1. Field of the Invention
The invention relates to the field of methodologies and apparatus used to characterize airway nitric oxide using different breath-hold times to characterize region-specific inflammation or pulmonary disease states.
2. Description of the Prior Art
Exhaled nitric oxide (NO) arises from both airway and alveolar regions of the lungs, which provides an opportunity to characterize region-specific inflammation. Current methodologies rely on vital capacity breathing maneuvers and controlled exhalation flow rates, which can be difficult to perform, especially for young children and individuals with compromised lung function. In addition, recent theoretical and experimental studies demonstrate that gas-phase axial diffusion of NO has a significant impact on the exhaled NO signal.
Nitric oxide can be detected in exhaled breath and is a potential noninvasive index of lung inflammation. Nitric oxide (NO) can be detected in the exhaled breath, and the concentration, FeNO, may reflect the inflammatory status of the lungs. However, NO exchange dynamics in the lungs are not yet fully developed, due primarily to the unique gas exchange characteristics of NO that include both airway and alveolar contributions. Current methodologies for partitioning exhaled NO into airway and alveolar contributions rely on vital capacity breathing maneuvers, which utilize a controlled exhalation flow rate, or a tidal breathing pattern. The techniques characterize the alveolar region with an alveolar concentration (CaNO) and the airway region with two parameters, the airway diffusing capacity (DawNO) and either the airway wall concentration (CawNO) or the maximum airway wall flux (J′awNO; equal to the product DawNO×CawNO). The techniques have been used successfully to characterize NO gas exchange dynamics for healthy subjects, as well as a wide range of lung diseases.
Important limitations remain in the characterization of NO exchange for both the experimental breathing maneuvers and the theoretical models. Early models of NO exchange neglected axial diffusion of NO in the gas phase, as well as the increasing cross-sectional area of the airway tree with increasing airway generation (i.e., trumpet shape). These simplifications generated errors in the estimation of CawNO and J′awNO. In addition, the variance of DawNO was larger than other parameters, and the accuracy depends on the residence time of the air in the airway compartment. A unique challenge in determining DawNO is the need to sample very low (<50 ml/s) exhalation flows. DawNO can only be measured if a very low exhalation flow rate (about 50 ml/s) is sampled. This requires long (about 20 s) and controlled (i.e., constant flow) exhalation phases, which can be difficult to perform for young children and subjects with compromised lung function. Importantly, DawNO may potentially provide unique structural information about the airways in lung diseases such as asthma. Accurate estimation of DawNO is particularly interesting because initial studies suggest that it is elevated in asthma but may be independent of steroid use, unlike FeNO and CawNO.
In addition, the most widely used analytical methods invoke a two-compartment model, which assumes a simple cylinder geometry to represent the airway anatomy, and neglects gas-phase axial diffusion of NO. Although these assumptions preserve mathematical simplicity, they likely generate significant errors in characterizing NO exchange.
Therefore, what is needed is 1) a technique that is simple to perform and focuses on determining airway NO parameters (CawNO, DawNO, and J′awNO), and 2) which compensates for important sources of errors, such as axial diffusion and the branching structure of the airway tree, that exist in some of the currently used methods to characterize NO exchange in the lung.